tbuckley/cabot-search huggingface dataset:
GLIOBLASTOMA: THE NEGLECTED CANCER IN THE TREATMENT REVOLUTION
Authors: Christopher Panks, Richard Clemmow
Journal: Neuro-Oncology (2023)

Abstract AIMS A paper written from the perspective of people living with glioblastoma and their carers: • Surveys the current treatment landscape in the UK • Questions why standard of care has not significantly changed in two decades • Argues for implementation of universal whole genome sequencing (WGS) for patients in line with a2018 government commitment that all patients in England with rare diseases should be offered WGS from2019 • Estimates how much WGS has been done METHOD OurBrainBank’s researcher gathered information from: • Freedom of information requests • Questions to health trusts and individual hospitals • Interviews with patients and carers • Interviews with clinicians, health administrators and researchers • A literature review RESULTS The paper estimates that up to the end of 2022 fewer than 1% of glioblastoma patients in England diagnosed since January 2019, (the date originally suggested for implementation of the government commitment), have had WGS of their tumours. This figure rises to only 1.3% of GBM patients diagnosed since April 2021, the date when the WGS policy began to be rolled out. CONCLUSIONS The government’s 2018 commitment to the implementation of WGS as applied to glioblastoma patients in England has failed by almost 2 orders of magnitude. The paper calls for this to be addressed through: • Universal frozen tissue storage • Universal genomic sequencing for all GBM patients where tissue is available • Specific, reliable GBM information on NHS and other offcial websites • Increased funding for translational research
MATHEMATICAL MODELLING OF SURVIVAL IN LOW GRADE GLIOMAS AT MALIGNANT TRANSFORMATION
Authors: Lily Tan, James Ruffle, Jeremy Rees, Michael Kosmin, Parahkev Nachev, Harpreet Hyare
Journal: Neuro-Oncology (2023)

Abstract AIMS Low grade gliomas (LGG) represent 14.6% of gliomas and may remain stable years after initial diagnosis. MRI features suggesting malignant transformation (MT) include enlargement of non-enhancing areas and increasing enhancement but have low specificity. We report the first stages of a deep learning model to predict survival using radiomic feature extraction at MT, clinical and molecular genetics. METHOD Retrospective analysis of all LGGs treated at our institution (2005 - 2020) with histology, molecular genetics and MRIs. 766 patients: 457 IDH mutant astrocytomas, 251 IDH mutant 1p19q co-deleted oligodendrogliomas and 58 other gliomas; 398 male, 368 female; mean age 51 years; range 16-89. MRIs underwent in-house tumour segmentation pipeline with radiomic feature extraction of whole tumour (wt), enhancing (enh), non-enhancing (ne) component and oedema components. RESULTS At MT, mean wt volume was 36404mm3 (SD 37213mm3) with mean 2D-diameter of 75.90mm (SD 27.23mm). Mean tissue compartmental volumes: enh 9539mm3 (SD 17578mm3), ne 26865mm3 (SD 33796mm3), and oedema 61067mm3 (SD 61535 mm3). 92 lesions contained no post-contrast enhancing tissue. Lesions were more commonly frontal or temporally based, with relative sparing of parietal and occipital lobes. No predilection for left or right hemisphere. CONCLUSIONS Majority of LGGs demonstrate contrast enhancing lesions at MT in a frontal or temporal spatial distribution with no hemispheric predilection. We plan to extract the MRI features at MT to build a survival model with clinical, treatment and molecular genetic data. Defining the radiological features at MT would enable prognostication and support clinical decision-making in this patient group.
ADULT HISTONE G34 MUTANT GLIOMAS - A SINGLE CENTRE EXPERIENCE OVER 10 YEARS
Authors: Ruth Obrocki, Ashirwad Merve, Jeremy Rees
Journal: Neuro-Oncology (2023)

Abstract AIMS Histone G-34-mutant (H3 G34) gliomas are rare, aggressive infiltrating tumours of the cerebral hemispheres and are classified as WHO grade 4 paediatric type diffuse high-grade glioma. They most commonly affect children and adolescents. We describe the clinicopathological characteristics of adult H3 G34-mutant gliomas seen at the National Hospital for Neurology and Neurosurgery over the last 10 years. METHOD We retrospectively analyzed clinic radiological data on all cases identified from the neuropathology database. Data were extracted on patient demographics, clinical and radiological features and outcome. RESULTS Six patients (2 male, 4 female) were identified, The median age of onset was 26 years (range 17-38 years). One patient presented with a Motor Neurone Disease type syndrome (progressive asymmetric spastic tetraparesis and bulbar symptoms), two with cognitive decline and three with symptoms of raised intracranial pressure. All tumours were supratentorial - 2 patients had mass lesions typical of a high-grade glioma, 1 patient had imaging features consistent with an intraventricular ependymoma. 3 patients had imaging findings that suggested a non-tumour diagnosis with extensive white matter disease more in keeping with an inflammatory demyelinating process or a leucodystrophy. The median overall survival was 23 Months (range 10 - 68 months). CONCLUSIONS Adult Histone G34-mutant gliomas have a variable presentation and are associated with a prognosis similar to other high-grade gliomas. The diagnosis should be considered in the differential of patients presenting with a predominantly white matter disorder. Multi-centre studies are needed to better delineate the phenotype and prognostic features.
AN EVALUATION OF THE USE OF TARGETED GENE PANELS TO IDENTIFY TARGETED TREATMENTS IN PATIENTS WITH BRAIN TUMOURS
Authors: Sana Hussain, Jane Hughes, Fi Collinson, Susan Short
Journal: Neuro-Oncology (2023)

Abstract AIMS • To assess the impact of undertaking targeted gene panel testing in brain tumour patients outside clinical studies • To assess if novel treatments have impacted management decisions and/or prognosis Testing for specific mutations in brain tumours may give opportunities for using targeted drugs. It is not well established how much patients benefit from this approach since routine panel testing has not been widely applied. METHOD We reviewed patients who had a known brain tumour and were referred to the early phase research clinic at St James’s for consideration of further treatment in the 6-month period [08/2022 – 02/2023]. We identified ten patients and reviewed their records in detail. Ad hoc testing was done on 6 patients, and SPARTA trial screening on 4 patients. RESULTS There were 7 males, 3 females with a mean age of 42 years (24-59). 3 were eligible for clinical trials using agents targeting mutations in the FGFR gene or RET fusion positive status (for the FIGHT 209 and TAPISTRY trials respectively). In 3 patients, there were no targetable mutations. One patient died whilst awaiting results and another is currently under palliative care. Two patients have outstanding molecular data. The data are too early to be able to assess effects on disease trajectory in any patient. CONCLUSIONS These data confirm that gene panel testing may suggest novel treatment options in a subset of brain tumour patients and support efforts to ensure that potentially suitable patients have access to appropriate molecular pathology and genomic testing.
MULTIDIMENSIONAL PROfiLES OF COGNITIVE DETERIORATION AND RECOVERY ASSOCIATED WITH GLIOBLASTOMA SURGERY
Authors: Yizhou Wan, Ajay Halai, Haiyan Zheng, Rohitashwa Sinha, Thomas Santarius, Richard Mair, Robert Morris, Matt Lambon-Ralph, Stephen J Price
Journal: Neuro-Oncology (2023)

Abstract AIMS Patients with glioblastoma suffer a high incidence of cognitive deficits. Cognition is the result of multiple neural mechanisms and glioblastoma is diffusely infiltrative with the capacity to invade multiple functional areas in the brain. We hypothesise that cognitive deterioration and recovery in these patients will be multidimensional in nature and therefore different components of cognition will show distinct recovery profiles following surgery. METHOD 28 patients with high-grade glioma, recruited at a single centre underwent preoperative (T0), early postoperative (within one week) (T1) and delayed (six to eight weeks) (T2) testing of their cognition with a neurocognitive screening tests; Oxford Cognitive Screen and Cambridge Attention, Memory and Perception Screen (OCS-Bridge) tool. Varimax principal component analysis was performed to determine if there are low-dimensional domains of cognition examined by the tests. Changes in cognitive scores between time points was calculated and correlated with principal component scores (PCs). RESULTS We found six principal components which explained 71% of the variance in OCS scores. and six different com- ponents explained 63% of the variance in Bridge scores. Cognitive deterioration was largely multidimensional with few significant correlations between PC change scores at T1 except tests loading on to visual field and spatial neglect. Cognitive recovery measured with T2 change scores were not significantly correlated between attention, praxis and language domains and between verbal working memory and visual memory and attention. CONCLUSIONS Longitudinal cognitive signatures of deterioration and recovery are heterogenous between patients. This high- lights the importance of targeting potentially distinct neural mechanisms for the rehabilitation of these patients.
AN ANALYSIS OF THE EFFECTIVENESS OF CURRENT PROVISION OF FATIGUE MANAGEMENT STRATEGIES WITHIN A NEURO-ONCOLOGY MDT CLINIC
Authors: Olivia Africa, Rebecca Clark, Bethany Sellwood
Journal: Neuro-Oncology (2023)

Abstract AIMS Cancer-related fatigue (CRF) is known to have a distressing impact on a patient’s function and quality of life, with as many as 9 out of 10 people with cancer (90%) experiencing CRF (Macmillan 2021). Management of CFR for patients with a Glioblastoma diagnosis is additionally complex given associated neurological affect. Physiotherapy and Occupational Therapy (PT &amp; OT) have an important role addressing CRF through interventions such as, graded exercise programmes, fatigue education, self-management strategies, cognitive rehab and sleep hygiene advice. Intervention varies depending on when the patient is being referred or logistics of the clinic setting. METHOD A 12-month review of the OT &amp; PT caseload (January 2022 – December 2022) is under evaluation to establish the number of patients reporting CRF at initial assessment or at follow up review. Clinic notes of patients reporting CRF have been reviewed to determine the oncological treatment time point that CRF was identified – pre, mid or post treatment. Data collection also includes patient and clinical characteristics, and the rehabilitation intervention type offered correlated to treatment phase. RESULTS 49 datasets are under evaluation, with the key aims to explore 1) the prevalence of CRF in patients referred to the Cancer Specialist OT and PT team, 2) correlation of reporting’s of CRF with treatment phase 3) the Rehabilitation Treatment Taxonomy deployed in the management of CRF. CONCLUSIONS Our evaluation will explore patients CRF needs and how they may change through the treatment pathway, leading to future recommendations for service quality improvement and implementation change.
PRO-DRUG NANOPARTICLES AS SYNERGISTIC DRUG COMBINATION CARRIERS FOR IDH1-WT GLIOBLASTOMA
Authors: Robert Cavanagh, Saif Baquain, Umut Can Oz, Amrita Sikder, Amr ElSherbeny, Cameron Alexander, Oren Scherman, Ruman Rahman
Journal: Neuro-Oncology (2023)

Abstract AIMS Synergistic combinations of doxorubicin and gemcitabine have been assessed for post-surgical treatment of IDH1 wild-type glioblastoma (GBM). As a complementary drug carrier, hyperbranched and micellar nanoparticles are being investigated to enable enhanced drug loading and sustained drug release. METHOD 2D and 3D spheroid in vitro models have been generated from patient-derived glioblastoma cells resected from tumour core and invasive margin. Drug combinations were screened using synergy quantification from the Chou and Talalay method and synergy mechanisms investigated using measures of caspase 3/6-mediated apoptosis and γH2AX-mediated DNA damage. Polymeric nanoparticles (PEG-PCL) loaded with Cy5 were tested for internalisation and subsequent endocytosis pathway determination. Both single drug and drug combinations are currently being incorporated into PEG-PCL nanoparticles for in vitro assessment of biocompatibility, cellular uptake and cytotoxicity. RESULTS Data demonstrate synergism with doxorubicin and gemcitabine combinations is obtained in a molar ratio de- pendent manner. Consistent with this, enhanced apoptosis and DNA damage is observed in a synergistic manner. PEG-PCL nanoparticles demonstrate effcient cellular uptake and are internalised via dynamin-dependent caveolae and clathrin endocytotic pathways. Interestingly, nanoparticle internalisation is substantially in- creased (approx. 50%) in invasive GBM cells relative to proliferative core cells. CONCLUSIONS Doxorubicin and gemcitabine has been identified as a synergistic drug combination with the potential for sustained drug release when combined with PEG-PCL nanoparticle formulations. Together, the data has provided a platform of knowledge that will enable translation to pre-clinical in vivo models.
PSYCHOLOGY EDUCATION WORKSHOPS ARE AN INNOVATIVE METHOD OF OFFERING PSYCHOLOGICAL INPUT TO A WIDER POPULATION
Authors: Victoria Hurwitz, Mark Groves, Carly Butler, Ellie Kostick, Jessica La, Sarah Hedges, Louise Delacroix, Aeron Suarez, Charlotte Robinson, Kazumi Chia, Lucy Brazil, Omar Al-Salihi, Angela Swampillai
Journal: Neuro-Oncology (2023)

Abstract AIMS People diagnosed with brain tumours are well recognised as needing psychological support. Service provision is limited and can be diffcult to gain engagement. Providing psychology education workshops aims to be inclusive, bring patients and loved ones together and offer an opportunity for peer support. METHOD Patients who had finished or were coming to the end of their current treatment were invited to attend a psychology education workshop. Their loved ones were also invited to attend via the patient’s invitation letter. A clinic code was set up to enable us to monitor who was invited, who attended and importantly who did not. This also aimed to integrate the workshop into standard of care on completion of treatment. Feedback was obtained from attendees at the end of the workshop verbally as well as offering the opportunity to give anonymous written feedback. RESULTS On average a third of people invited attended each group. Half of these attended with one or more loved ones. 100% of attendees found the workshop helpful. Feedback included “Useful to realise that my emotions are similar to his” – Carer and “Having the shared experience of being here with (loved one) has started to open things up for us as a family” – Family member. CONCLUSIONS Patients and carers valued the workshop. This format offered a more accessible introduction to psychology. The workshop was enough to provide some patients and carers with strategies to look after their psychological well-being and served as a method of identifying those with greater need.
STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES FROM GASTROINTESTINAL PRIMARIES: ANALYSIS OF OUTCOMES
Authors: Sophie Lynch, Omar Al-Salihi, Vishal Manik, Asad Qureshi, Sheila Hassan, Samantha Forner, Meeta Durve, Kazumi Chia
Journal: Neuro-Oncology (2023)

Abstract AIMS Brain metastases from gastrointestinal primaries are uncommon with poor reported outcomes following SRS. We evaluated clinical outcomes for patients diagnosed with metastatic brain tumours from a gastrointestinal primary treated with stereotactic radiosurgery (SRS). METHOD A single institutional retrospective review of patients treated with LINAC-based SRS at our institution between 2017 and 2022. Median survival was calculated from the time of SRS. RESULTS A total of 24 patients were treated with primary malignancy locations as follows: 10 colon, 7 rectum and 7 oesophageal. Median survival was 6.4 months for the overall cohort and 4.5 months for colon, 6.1 months for rectum and 14 months for oesophagus. 44% and 14% of patients had undergone surgical resection with colorectal cancer (CRC) and oesophageal cancer respectively. Median survival in CRC patients receiving SRS post-operatively was 6.8 months compared with 11.5 months for patients with non-gastrointestinal primaries. Time from diagnosis of the primary malignancy to diagnosis of brain metastases showed an inverse correlation with survival: 48 months colon, 21 months rectum and 13 months oesophagus. Compared to oesophageal patients, CRC patients were more likely to have extra-cranial disease at the time of SRS (57% vs. 18%). CONCLUSIONS Survival after SRS to brain metastases from gastrointestinal primaries is poor, but we demonstrate important differences in outcome depending on the location of the primary malignancy. Oesophageal cancer patients had the best survival with colon cancer patients having the worst. Although our findings are likely to influenced by patient selection bias, these differences are worthy of further investigation.
Single‐Molecule Dendritic MRI Nanoprobes Reveal the Size‐Dependent Tumor Entrance
Authors: Huiming Ren, Qiuhui Hu, Jiajia Yang, Xiaoxuan Zhou, Xiangrui Liu, Jianbin Tang, Hongjie Hu, Youqing Shen, Zhuxian Zhou
Journal: Advanced Healthcare Materials (2023)

The tumor entrance of drug delivery systems, including therapeutic proteins and nanomedicine, plays an essential role in affecting the treatment outcome. Nanoparticle size is a critical but contradictory factor in making a trade-off among blood circulation, tumor accumulation, and penetration. Here, this work designs a series of single-molecule gadolinium (Gd)-based magnetic resonance imaging (MRI) nanoprobes with well-defined sizes to precisely explore the size-dependent tumor entrance in vivo. The MRI nanoprobes obtained by divergent synthesis contain a core molecule of macrocyclic Gd(III)-chelate and different layers of dendritic lysine units, mimicking globular protein. This work finds that the r
THE KYNURENINE PATHWAY AND ITS ROLE IN GLIOBLASTOMA CELL MIGRATION
Authors: Diana Sirnikova, Johannes Reynisson, Anke Brüning-Richardson, Catherine Kirby
Journal: Neuro-Oncology (2023)

Abstract AIMS The kynurenine (Kyn) pathway plays an important role in the pathogenesis of many cancers including glioblastomas (GBMs). The enzymes, indoleamine-2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (TDO2), regulate the first and rate-limiting step resulting in the formation of N-formyl-kynurenine, which is then readily converted into Kyn by kynurenine formaldehyde. Cancers expressing the IDO1 and TDO2 enzymes can produce immunosuppressive tryptophan metabolites that compromise the host immune system leading to poor patient prognosis. The inhibitors TD12, TD18 and TD34 were recently developed due to the lack of TDO2 and IDO1/TDO2 inhibitors, of which TD34 can block both IDO1 and TDO2 activity. Here, we investigated the ability of these novel inhibitors to also target cell migration in GBM as part of our ongoing research interest in this area. METHOD Two established brain tumour cell lines, U87 and U251 and one patient-derived cell line, E55, were used to determine IC50 values and anti-migratory concentrations by MTT for application in 2D and 3D migration/invasion assays. RESULTS Cell migration in all cell lines was significantly reduced in the presence of the TD12, TD18 and TD34 inhibitors. E55 appeared to be 100-fold more sensitive to drug activity; immunofluorescence analysis indicates changes in the actin cytoskeleton and cell adhesion CONCLUSIONS Initial results suggest that TDO2 and the IDO1 enzymes play also a role in cell migration in GBM and provide further evidence for the involvement of the Kyn pathway in the pathology of GBMs. This also supports the application of inhibitors targeting TDO2 and IDO1 as novel complementary treatment options in GBM.
BEHAVIOURAL TESTING OF SENSORI-MOTOR FUNCTION IN AWAKE CRANIOTOMY; A LITERATURE REVIEW
Authors: Sara Cooper, Rohit Sinha, Elisa Stephenson, Seonaid Ewan, Ryan Mathew
Journal: Neuro-Oncology (2023)

Abstract AIMS Evaluate how sensori-motor (SM) testing is performed in awake craniotomy (AC) in the literature. Compare SM testing methods and their related outcomes. METHOD Literature search from 1995- 2019 in OVID Medline, Embase, PsychInfo, CINAHL and Web Of Science using all permutations of MESH terms “brain tumour” “awake craniotomy” “sensory” “motor” “testing”. 11671 articles were screened and 28 included based on suffcient detail of the tasks and intraoperative processes that would allow for evaluation. RESULTS SM testing is used to preserve function in AC when tumours involve or neighbour eloquent cortical structures sub serving movement. It is also used to identify subcortical tracts such as corticospinal and frontostriatal, as well as and the negative motor network. There is broad variation in how SM testing is conducted in different centres, with no standardisation. The most common strategies were: •Simple gross movement of contralateral limbs (n= 17) e.g., hand open/closing. •Functional movement (n=5) e.g., grasping object •Standardised tests (n= 3) including the Hand Manipulation Task and Sensory-Motor Profile awake •Patient at rest observed for positive motor responses or patient reported sensory changes (n= 2). CONCLUSIONS Multiple different intra-operative strategies exist for the preservation of sensori-motor function in awake craniotomy. Benefits of the over-arching AC strategy for SM preservation is frequently demonstrated. However, comparison and optimisation between strategies is hindered by heterogenous study objectives and outcomes reported. A core testing and outcome set may be useful to standardise, optimise and compare so that maximal patient benefit and functional preservation can be achieved.
A NOVEL THERAPEUTICS ACCELERATOR TO SUPPORT A STRONGER BRAIN TUMOUR TREATMENT PIPELINE
Authors: Nicky Huskens, Charlotte Aitken, Katie Bushby
Journal: Neuro-Oncology (2023)

Abstract AIMS Despite several encouraging pre-clinical studies, few therapeutics make it to successful human trials. There is a need for a stronger new treatment pipeline to improve outcomes for patients with brain tumours. The Tessa Jowell Brain Cancer Mission have launched the Brain Tumour Research Novel Therapeutics Accelerator (BTR- NTA) to provide bespoke advice and support to scientists and help position their therapeutic along a realistic pathway to clinical trials METHOD The BTR-NTA programme is supported by an international committee of brain tumour, pre-clinical science, and pharmaceutical experts who meet twice yearly to review up to five novel brain tumour therapeutics. Both academic and industry applicants, at any stage of pre-clinical or clinical work, can apply and submit their work to date before meeting with the BTR-NTA committee to discuss their therapeutic and progress. The committee then provides a written feedback report with advice and recommendations on next steps. The committee will also facilitate connections with industry partners and funders where possible. RESULTS It is hoped that BTR-NTA will provide benefits for the whole brain tumour community by: increasing the number of brain tumour therapeutics reaching patients; providing applicants with constructive feedback so that avoidable pitfalls can be overcome; strengthening international relationships between academics, industry, government, and regulatory bodies; and de-risking investment into brain tumour therapeutics for funders. CONCLUSIONS The first BTR-NTA meeting will be held in November 2023, with applications opening mid-2023.